Laterality and region-specific tau phosphorylation correlate with PTSD-related behavioral traits in rats exposed to repetitive low-level blast

Acta Neuropathologica Communications

Gregory A. Elder¹  Stephen T. Ahlers²  Usmah Kawoos³  Rania Abutarboush³  Dara L. Dickstein⁴  Miguel A. Gama Sosa⁵  David G. Cook⁶  Patrick R. Hof⁷  Dylan Pryor⁸  Alena Otero-Pagan⁸  Gissel M. Perez⁸  Georgina Perez Garcia⁹  Sam Gandy^1,10  Rita De Gasperi^1,11 

[1] Department of Neurology, Icahn School of Medicine At Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Department of Psychiatry, Icahn School of Medicine At Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Mount Sinai Alzheimer’s Disease Research Center and Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine At Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Neurology Service, James J. Peters Department of Veterans Affairs Medical Center, Neurology Service (3E16), 130 West Kingsbridge Road, 10468, Bronx, NY, USA;Department of Neurotrauma, Naval Medical Research Center, 503 Robert Grant Avenue, 20910, Silver Spring, MD, USA;Department of Neurotrauma, Naval Medical Research Center, 503 Robert Grant Avenue, 20910, Silver Spring, MD, USA;The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA;Department of Pathology, Uniformed Services University of Health Sciences, 4301 Jones Bridge Rd., 20814, Bethesda, MD, USA;Center for Neuroscience and Regenerative Medicine, Uniformed Services University of Health Sciences, 4301 Jones Bridge Rd., 20814, Bethesda, MD, USA;Department of Psychiatry, Icahn School of Medicine At Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;General Medical Research Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, 10468, Bronx, NY, USA;Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, 1660 S Columbian Way, 98108, Seattle, WA, USA;Department of Medicine, University of Washington, 1959 NE Pacific St, 98195, Seattle, WA, USA;Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine At Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Department of Geriatrics and Palliative Care, Icahn School of Medicine At Mount Sinai, One Gustave Levy, 10029, New York, NY, USA;Mount Sinai Alzheimer’s Disease Research Center and Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine At Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, 10468, Bronx, NY, USA;Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, 10468, Bronx, NY, USA;Department of Neurology, Icahn School of Medicine At Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, 10468, Bronx, NY, USA;Department of Neurology, Icahn School of Medicine At Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Department of Psychiatry, Icahn School of Medicine At Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Mount Sinai Alzheimer’s Disease Research Center and Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine At Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;Barbara and Maurice A. Deane Center for Wellness and Cognitive Health, and Mount Sinai NFL Neurological Care Center, Icahn School of Medicine At Mount Sinai, 5 East 98th Street, 10029, New York, NY, USA;Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, 10468, Bronx, NY, USA;Department of Psychiatry, Icahn School of Medicine At Mount Sinai, One Gustave Levy Place, 10029, New York, NY, USA;

关键词: Animal model;    Behavior;    Blast;    Laterality;    Rat;    Tau;    Traumatic brain injury;   

DOI  :  10.1186/s40478-021-01128-3

来源: Springer

【 摘 要 】

Military veterans who experience blast-related traumatic brain injuries often suffer from chronic cognitive and neurobehavioral syndromes. Reports of abnormal tau processing following blast injury have raised concerns that some cases may have a neurodegenerative basis. Rats exposed to repetitive low-level blast exhibit chronic neurobehavioral traits and accumulate tau phosphorylated at threonine 181 (Thr181). Using data previously reported in separate studies we tested the hypothesis that region-specific patterns of Thr181 phosphorylation correlate with behavioral measures also previously determined and reported in the same animals. Elevated p-tau Thr181 in anterior neocortical regions and right hippocampus correlated with anxiety as well as fear learning and novel object localization. There were no correlations with levels in amygdala or posterior neocortical regions. Particularly striking were asymmetrical effects on the right and left hippocampus. No systematic variation in head orientation toward the blast wave seems to explain the laterality. Levels did not correlate with behavioral measures of hyperarousal. Results were specific to Thr181 in that no correlations were observed for three other phospho-acceptor sites (threonine 231, serine 396, and serine 404). No consistent correlations were linked with total tau. These correlations are significant in suggesting that p-tau accumulation in anterior neocortical regions and the hippocampus may lead to disinhibited amygdala function without p-tau elevation in the amygdala itself. They also suggest an association linking blast injury with tauopathy, which has implications for understanding the relationship of chronic blast-related neurobehavioral syndromes in humans to neurodegenerative diseases.

【 授权许可】

CC BY